Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment of advanced gastric or gastroesophageal junction adenocarcinoma: patient-reported outcomes in the RATIONALE-305 study.

IF 2.4 4区医学 Q1 MEDICINE, GENERAL & INTERNAL

Current Medical Research and Opinion Pub Date : 2025-06-18 DOI:10.1080/03007995.2025.2501588

Marcia Cruz-Correa, Rui-Hua Xu, Markus Moehler, Do-Youn Oh, Ken Kato, David Spigel, Hendrik-Tobias Arkenau, Josep Tabernero, Anastasia V Zimina, Yuxian Bai, Jianhua Shi, Keun-Wook Lee, Hidekazu Hirano, Lucjan Wyrwicz, Roberto Pazo Cid, Hui Xu, Tao Sheng, Gisoo Barnes

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引用次数: 0

Abstract

Objective: RATIONALE-305 (NCT03777657) demonstrated that tislelizumab plus chemotherapy statistically improved overall survival versus placebo plus chemotherapy as first-line treatment in patients with advanced gastric/gastroesophageal junction adenocarcinoma (GC/GEJC). This analysis examined patient-reported outcomes (PROs) at final analysis.

Methods: Adults with previously untreated, unresectable, or metastatic GC/GEJC were randomized (1:1) to tislelizumab or placebo intravenously once every 3 weeks plus chemotherapy. PROs assessed health-related quality of life (HRQoL) using EORTC QLQ-C30 and EORTC QLQ-STO22. A mixed model for repeated measures was used for PRO endpoints at treatment cycles 4 and 6, and time to deterioration was analyzed.

Results: Tislelizumab arm had improved outcomes over placebo arm in least-squares (LS) mean change from baseline to cycle 6 for QLQ-C30 global health status/quality of life (GHS/QoL) (LS mean difference, 2.52 [95% CI: 0.29-4.74]), physical functioning (2.46 [0.49-4.43]), fatigue (-3.01 [-5.78 to -0.24]), and STO22 index score (-1.62 [-3.12 to -0.12]) as well as maintenance of upper gastrointestinal symptoms (-1.74 [-3.55-0.06]) and pain/discomfort (-1.88 [-4.03-0.27]). Patients receiving tislelizumab plus chemotherapy had a lower risk for deterioration of GHS/QoL (hazard ratio 0.77 [95% CI: 0.60-0.98]), physical functioning (0.72 [0.57-0.92]), STO22 index score (0.64 [0.45-0.92]), pain/discomfort (0.74 [0.58-0.96]), and upper gastrointestinal symptoms (0.73 [0.56-0.95]).

Conclusions: Advanced GC/GEJC patients treated with tislelizumab plus chemotherapy versus placebo plus chemotherapy in first-line had sustained and improved HRQoL. These results, along with previous efficacy and safety data, support tislelizumab plus chemotherapy as a first-line treatment option for GC/GEJC.

Trial registration: The RATIONALE-305 trial is registered on ClinicalTrials.gov (ClinicalTrials.gov identifier: NCT03777657).ClinicalTrials.gov identifier: NCT03777657.

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Tislelizumab加化疗与安慰剂加化疗作为晚期胃或胃食管交界处腺癌的一线治疗：RATIONALE-305研究中患者报告的结果

目的：rational -305 （NCT03777657）表明，与安慰剂加化疗相比，tislelizumab加化疗作为晚期胃/胃食管结腺癌（GC/GEJC）患者的一线治疗，在统计学上提高了总生存率。该分析在最终分析中检查了患者报告的结果（PROs）。方法：先前未经治疗，不可切除或转移性GC/GEJC的成人随机（1:1），每3周静脉注射一次tislelizumab或安慰剂加化疗。专业人员使用EORTC QLQ-C30和EORTC QLQ-STO22评估健康相关生活质量（HRQoL）。重复测量的混合模型用于治疗周期4和6的PRO终点，并分析恶化时间。结果：与安慰剂组相比，Tislelizumab组在QLQ-C30总体健康状况/生活质量（GHS/QoL）（LS平均差异2.52 [95% CI: 0.29-4.74]）、身体功能（2.46[0.49-4.43]）、疲劳（-3.01[-5.78至-0.24]）和STO22指数评分（-1.62[-3.12至-0.12]）以及上胃肠道症状维持（-1.74[-3.55至0.06]）和疼痛/不适（-1.88[-4.03至0.27]）方面从基线到第6周期的最小二乘（LS）平均变化改善。接受替利单抗联合化疗的患者GHS/QoL（风险比0.77 [95% CI: 0.60-0.98]）、身体功能（0.72[0.57-0.92]）、STO22指数评分（0.64[0.45-0.92]）、疼痛/不适（0.74[0.58-0.96]）和上消化道症状（0.73[0.56-0.95]）恶化的风险较低。结论：晚期GC/GEJC患者在一线接受tislelizumab联合化疗与安慰剂联合化疗相比，HRQoL持续改善。这些结果，连同先前的疗效和安全性数据，支持tislelizumab加化疗作为GC/GEJC的一线治疗选择。试验注册：RATIONALE-305试验在ClinicalTrials.gov上注册（ClinicalTrials.gov标识符：NCT03777657）。

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来源期刊

Current Medical Research and Opinion 医学-医学：内科

CiteScore

4.40

自引率

4.30%

发文量

247

审稿时长

3-8 weeks

期刊介绍： Current Medical Research and Opinion is a MEDLINE-indexed, peer-reviewed, international journal for the rapid publication of original research on new and existing drugs and therapies, Phase II-IV studies, and post-marketing investigations. Equivalence, safety and efficacy/effectiveness studies are especially encouraged. Preclinical, Phase I, pharmacoeconomic, outcomes and quality of life studies may also be considered if there is clear clinical relevance